Molecular modeling reveals the inhibition mechanism and binding mode of ursolic acid to TLR4-MD2

Medzhitov, 1997, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity, Nature, 388, 394, 10.1038/41131 Gay, 2007, Structure and function of Toll receptors and their ligands, Annu. Rev. Biochem., 76, 141, 10.1146/annurev.biochem.76.060305.151318 Roach, 2005, The evolution of vertebrate Toll-like receptors, Proc. Nat. Acad. Sci. USA, 102, 9577, 10.1073/pnas.0502272102 Matsushima, 2007, Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors, BMC Genom., 8, 124, 10.1186/1471-2164-8-124 Viriyakosol, 2001, MD-2 binds to bacterial lipopolysaccharide, J. Biol. Chem., 276, 38044, 10.1074/jbc.M105228200 Shimazu, 1999, MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4, J. Experim. Med., 189, 1777, 10.1084/jem.189.11.1777 Kim, 2007, Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran, Cell, 130, 906, 10.1016/j.cell.2007.08.002 Wang, 2016, TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS, Proc. Nat. Acad. Sci. USA, 113, E884, 10.1073/pnas.1525639113 De Paola, 2016, Synthetic and natural small molecule TLR4 antagonists inhibit motoneuron death in cultures from ALS mouse model, Pharmacol. Res., 103, 180, 10.1016/j.phrs.2015.11.020 Chebrolu, 2015, Species and mediator specific TLR4 antagonism in primary human and murine immune cells by betaGlcN(1<–>1)alphaGlc based lipid A mimetics, Mol. Immunol., 67, 636, 10.1016/j.molimm.2015.07.037 Denner, 2015, Treatment of Ebola virus infections with inhibitors of TLR4, Medical hypotheses, 85, 253, 10.1016/j.mehy.2015.05.009 Huggins, 2015, A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms development, Atherosclerosis, 242, 563, 10.1016/j.atherosclerosis.2015.08.010 Sestito, 2017, Amphiphilic guanidinocalixarenes inhibit lipopolysaccharide (LPS)- and lectin-stimulated toll-like receptor 4 (TLR4) signaling, J. Med. Chem., 60, 4882, 10.1021/acs.jmedchem.7b00095 Neve, 2014, Euodenine A: a small-molecule agonist of human TLR4, J. Med. Chem., 57, 1252, 10.1021/jm401321v Wu, 2016, Engeletin alleviates lipopolysaccharide-induced endometritis in mice by inhibiting TLR4-mediated NF-kappaB activation, J. Agric. food Chem., 64, 6171, 10.1021/acs.jafc.6b02304 Rodriguez Lavado, 2014, Trehalose- and glucose-derived glycoamphiphiles: small-molecule and nanoparticle Toll-like receptor 4 (TLR4) modulators, J. Med. Chem., 57, 9105, 10.1021/jm501182w Artner, 2013, Conformationally constrained lipid A mimetics for exploration of structural basis of TLR4/MD-2 activation by lipopolysaccharide, ACS Chem. Biol., 8, 2423, 10.1021/cb4003199 Bao, 2015, Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes, J. Agric. Food Chem., 63, 2811, 10.1021/jf505531w Lu, 2015, N(6)-(2-hydroxyethyl)adenosine in the medicinal mushroom cordyceps cicadae attenuates lipopolysaccharide-stimulated pro-inflammatory responses by suppressing TLR4-mediated NF-kappaB signaling pathways, J. Nat. Prod., 78, 2452, 10.1021/acs.jnatprod.5b00573 Malgorzata-Miller, 2016, Bartonella quintana lipopolysaccharide (LPS): structure and characteristics of a potent TLR4 antagonist for in-vitro and in-vivo applications, Sci. Rep., 6, 34221, 10.1038/srep34221 Jang, 2014, Ursolic acid isolated from the seed of cornus officinalis ameliorates colitis in mice by inhibiting the binding of lipopolysaccharide to Toll-like receptor 4 on macrophages, J. Agric. Food Chem., 62, 9711, 10.1021/jf501487v Morris, 2009, Autodock4 and autodocktools4: automated docking with selective receptor flexibility, J. Comput. Chem., 30, 2785, 10.1002/jcc.21256 Hu, 2010, Molecular dynamics simulations of 2-amino-6-arylsulphonylbenzonitriles analogues as HIV inhibitors: interaction modes and binding free energies, Chem. Biol. Drug Des., 76, 518, 10.1111/j.1747-0285.2010.01028.x Morris, 1996, Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4, J. Comput.-Aided Mol. Des., 10, 293, 10.1007/BF00124499 Dong, 2013, Oroxylin A inhibits hemolysis via hindering the self-assembly of alpha-hemolysin heptameric transmembrane pore, PLoS Comput. Biol., 9, e1002869, 10.1371/journal.pcbi.1002869 Niu, 2013, Molecular insight into the inhibition mechanism of cyrtominetin to alpha-hemolysin by molecular dynamics simulation, Eur. J. Med. Chem., 62, 320, 10.1016/j.ejmech.2013.01.008 Qiu, 2013, Molecular modeling reveals the novel inhibition mechanism and binding mode of three natural compounds to staphylococcal alpha-hemolysin, PloS One, 8, e80197, 10.1371/journal.pone.0080197 Hess, 2008, GROMACS 4: algorithms for highly efficient load-balanced, and scalable molecular simulation, J. Chem. Theory Comput., 4, 435, 10.1021/ct700301q Punkvang, 2010, Investigating the structural basis of arylamides to improve potency against M. tuberculosis strain through molecular dynamics simulations, Eur. J. Med. Chem., 45, 5585, 10.1016/j.ejmech.2010.09.008 Schaffner-Barbero, 2010, Insights into nucleotide recognition by cell division protein FtsZ from a mant-GTP competition assay and molecular dynamics, Biochemistry, 49, 10458, 10.1021/bi101577p